Rotaviruses have emerged as the single most important etiologic agents of severe diarrhea of infants and young children in both developed and developing countries. Thus, the need for an effective rotavirus vaccine is clear. The goal of such a vaccine is to prevent severe rotavirus diarrhea during the first 2 years of life when this disease is most serious. An animal rotavirus strain, rhesus rotavirus (RRV), is under intensive study in LID as a vaccine candidate. This simian rotavirus has not been recovered under natural conditions from man and is thus not a virus of the human heritage. Although the genes of RRV exhibit significant divergence in sequence from the corresponding genes of human rotaviruses, this simian rotavirus is similar if not identical to human rotavirus type 3 when tested by neutralization. The RRV vaccine was found to be satisfactorily antigenic as well as non-reactogenic in adults and children. However, in several pediatric studies a transient febrile response and/or loose stools occurred when 6-12 month old infants were fed 10-5PFU of virus. At a dose of 10-4PFU the RRV retained its antigenicity in infants less than 6 months of age but did not cause significant reactions. Analysis of prevaccination serum RRV neutralizing antibody titers in several populations, some in which reactions occurred and some in which reactions did not occur, suggested that the reactions might be related to the absence of serum antibody to RRV. Thus, prevaccination serum RRV antibodies may modify clinical reactions to RRV vaccine without significantly affecting infectivity or antigenicity. Following the identification of a safe antigenic dose of vaccine several phase two double blind field trials were initiated with various collaborators in the U.S. and other parts of the world in order to assess the efficacy of this vaccine in infants under 6 months of age.